Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.
Melissa Milazzoa , Antonio Chaves-Sanjuana,g, Luca Brogginib , Filippo Ferric,d,f, Carlo Palizzottoc , Silvia Ferroh , Eric  Zinic,d,e, Stefano Ricagnoa,b
a Department of Biosciences, Università degli Studi di Milano, Milan, Italy
b Institute of Molecular and Translational Cardiology, IRCCS Policlinico San Donato, Milan, Italy
c AniCura Istituto Veterinario Novara, Granozzo con Monticello, NO, Italy
d Department of Animal Medicine, Production and Health, University of Padova, Legnaro, PD Italy
e Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
f Studio Veterinario Associato Vet2Vet di Ferri e Porporato, Orbassano, TO, Italy
g CRC Fondazione Romeo e Enrica Invernizzi and NOLIMITS, Università degli Studi di Milano, 20133, Milan, Italy
h Department of Comparative Biomedicine and Food Sciences, University of Padova, Legnaro, Padova, Italy

Main Body of the Abstract
AA-amyloidosis is caused by the misfolding and aggregation of Serum Amyloid A in the extracellular matrix, leading to organ failure. The disease prevalence in captive cats and cheetahs was reported in the literature before, plausibly caused by horizontal transmission (Ferri et al. PLoS One 2023  10.1371/journal.pone.0281822). In cats, the kidneys, spleen, and liver are the most affected organs.  This project focuses on cryo-EM structural analyses of ex-vivo samples extracted post-mortem from diseased cats, who therefore constitute a model for the pathology. Intriguingly, post-mortem analysis revealed an unparalleled distribution of AA amyloids present in the majority of the internal organs (Moccia et al. PLoS One  2023 10.1371/journal.pone.0293892).  Here we report two AA-amyloid fibril structures extracted from the heart of a deceased cat, with multiple organ deposition. Interestingly, three different polymorphisms coexist in the same sample, named polymorphisms I, II, and III, which represent 80%, 15%, and 5% of the sample, respectively. The amyloid folds of the three polymorphisms are totally different, with polymorphisms I and II composed of two protofilaments and characterised by C2 symmetry, and polymorphism III composed of three protofilaments and presenting C1 symmetry. Moreover, the polypeptide arrangement is also extremely different between polymorphisms, and totally independent from cat, mouse, and human AA-amyloid structures previously deposited (Schulte et al. Nat Commun. 2022 10.1038/s41467-022-34743-2; Bansal et al.  2 Nat Commun. 2021 10.1038/s41467-021-21129-z; Liberta et al. Nat Commun. 2019 10.1038/s41467-019- 09033-z).  The project ultimately aims to understand the molecular mechanisms underlying AA-fibril amyloidogenesis by comparing structures from different organs and species.

**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Melissa Milazzo^a^ , Antonio Chaves-Sanjuan^a,g^, Luca Broggini^b^ , Filippo Ferri^c,d,f^, Carlo Palizzotto^c^ , Silvia Ferro^h^ , Eric  Zini^c,d,e^, Stefano Ricagno^a,b^
^a^ Department of Biosciences, Università degli Studi di Milano, Milan, Italy
^b^ Institute of Molecular and Translational Cardiology, IRCCS Policlinico San Donato, Milan, Italy
^c^ AniCura Istituto Veterinario Novara, Granozzo con Monticello, NO, Italy
^d^ Department of Animal Medicine, Production and Health, University of Padova, Legnaro, PD Italy
^e^ Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
^f^ Studio Veterinario Associato Vet2Vet di Ferri e Porporato, Orbassano, TO, Italy
^g^ CRC Fondazione Romeo e Enrica Invernizzi and NOLIMITS, Università degli Studi di Milano, 20133, Milan, Italy
^h^ Department of Comparative Biomedicine and Food Sciences, University of Padova, Legnaro, Padova, Italy

**Main Body of the Abstract**
AA-amyloidosis is caused by the misfolding and aggregation of Serum Amyloid A in the extracellular matrix, leading to organ failure. The disease prevalence in captive cats and cheetahs was reported in the literature before, plausibly caused by horizontal transmission (Ferri et al. PLoS One 2023  10.1371/journal.pone.0281822). In cats, the kidneys, spleen, and liver are the most affected organs.  This project focuses on cryo-EM structural analyses of ex-vivo samples extracted post-mortem from diseased cats, who therefore constitute a model for the pathology. Intriguingly, post-mortem analysis revealed an unparalleled distribution of AA amyloids present in the majority of the internal organs (Moccia et al. PLoS One  2023 10.1371/journal.pone.0293892).  Here we report two AA-amyloid fibril structures extracted from the heart of a deceased cat, with multiple organ deposition. Interestingly, three different polymorphisms coexist in the same sample, named polymorphisms I, II, and III, which represent 80%, 15%, and 5% of the sample, respectively. The amyloid folds of the three polymorphisms are totally different, with polymorphisms I and II composed of two protofilaments and characterised by C2 symmetry, and polymorphism III composed of three protofilaments and presenting C1 symmetry. Moreover, the polypeptide arrangement is also extremely different between polymorphisms, and totally independent from cat, mouse, and human AA-amyloid structures previously deposited (Schulte et al. Nat Commun. 2022 10.1038/s41467-022-34743-2; Bansal et al.  2 Nat Commun. 2021 10.1038/s41467-021-21129-z; Liberta et al. Nat Commun. 2019 10.1038/s41467-019- 09033-z).  The project ultimately aims to understand the molecular mechanisms underlying AA-fibril amyloidogenesis by comparing structures from different organs and species.

Cryo-EM structural characterisation of toxic protein aggregates in a cat affected by AA Amyloidosis PC4 (#84)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.